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Amino acids 395-416 in DNA binding domain of STAT4 is involved in IL-12-induced nuclear import of STAT4
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- Author:
- No author available
- Journal Title:
- Acta Physiologica Sinica
- Issue:
- 4
- DOI:
- No doi available
- Key Word:
- 核移位;核定位信号;信号转导和转录活化蛋白4
Abstract： 本研究旨在探讨信号转导和转录活化蛋白4 (signal transducer and activator of transcription 4,STAT4)受白介素-12 (interleukin-12,IL-12)剌激后移位入细胞核的机制.对STATs家族成员进行同源性比对分析结果显示,STAT4的DNA结合域的395～416位氨基酸残基序列可能具有二聚体特异性核定化信号(dimer-specific nuclear localization signal,dsNLS)功能.有鉴于此,本研究以pEGFP-C1为表达载体,分别构建了pEGFP-STAT4质粒、缺失395～416位氨基酸残基序列的缺失型STAT4质粒(pEGFP-STAT4-Del)、将SV40大T抗原上经典的NLS核酸序列插入表达载体的阳性对照质粒(pEGFP-NLS)和将缺失型STAT4插入pEGFP-NLS的pEGFP-NLS-STAT4-Del质粒.将这些质粒瞬时转染宫颈癌腺癌细胞系Caski细胞,经过IL-12刺激,发现野生型STAT4移位入细胞核,而缺失型STAT4分布在细胞浆中；进一步用leptomycin B处理,IL-12再刺激后野生型STAT4被滞留于细胞核中,而缺失型STAT4仍然分布在胞浆中；将NLS插入缺失型STAT4,能恢复缺失型STAT4的核移位.以上结果说明野生型STAT4在1L-12刺激下能移位入细胞核,其入核机制是在其DNA结合域的395～416位氨基酸残基序列具有dsNLS功能,能介导活化的STAT4移位入细胞核.
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